According to the statistics of World Health Organization (WHO), 10 million people have suffered from malignant tumors around the world each year, among which about 6 million people have died from the malignant tumors, accounting for 12% of the global death toll. In China, there have been 1.8 million new patients with a malignant tumor each year, causing a death toll of 1.4 million with 1.3 patients dying from malignant tumors every 3 minutes; moreover, the incidence rate of the malignant tumors has shown a trend of sharp increase.
Imaging technology is one of tools indispensable to tumor research and clinic therapy thereof. Currently, there have been a variety of non-fluorescent in vivo imaging technologies such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), etc. The biggest problem with these methods is that the specificity and sensitivity are insufficient. Visible light imaging technologies have a high resolution for tumor detection and give signals which are capable of providing molecular information of a biological tissue and showing changes of important physiological parameters, among which a fluorescent imaging technology labels tumor cells with an imaging agent, thus imaging the tumor cells and achieving a better effect of resolution. A cyanine dye compound may be used as a tumor imaging agent, and the instrument applied for its imaging does not need invasion into an organism, which makes it possible to achieve tumor imaging with an ordinary LED screen.
However, most of cyanine dyes possess no selectivity to a specific organ and tissue, and thus have to be connected to bioactive carriers such as proteins, polypeptides, lipids, saccharides and other markers such that the dyes are possible to be combined with a target to enter a specific region. Therefore, the cyanine dyes which may be used as imaging agents currently have a general drawback of insufficient targeting, which tend to retain in the live and generally have a high background value in vivo.
In addition, due to the capability of producing reactive oxygen, the cyanine dye may also be used as a photosensitizer in photodynamic therapy (PDT) for tumor treatment. PDT is a novel therapy for selectively treating a disease such as tumor through a photodynamic reaction in combination with a photosensitizer. PDT is a therapeutic method with no systemic, organ or tissue toxicity, and is noninvasive, which may be reused as a main or an auxiliary means. However, cyanine dyes with different structures have different properties, and also have different roles in the PDT therapy. Currently, the commonly-used merocyanine-based cyanine dye is OXO or MC540, with the former having no strong stability and being prone to be used as a photosensitizer, while the latter having poor photosensitization and being more suitable for detection of tumor cells.
Therefore, the development of a dual-function agent which can have both functions of a photosensitizer and an imaging agent has become the research focus. Conjugates formed by the conjugation of a cyanine dye with a photosensitizer have a good photosensitivity and imaging effect, and are very suitable for use as a dual-function agent in photodynamic therapy. Such compounds includes a biochip made by binding of a cyanine dye Cy5 to an antibody, or a cyanine dye-peptide conjugate, etc. However, for these compounds, the antibody is used as a marker, which would influence the half-life of immunogen and plasma. More importantly, due to the specificity for the combination of a marker and a target molecule, use of such a conjugate is greatly limited.
In summary, a tumor imaging agent having good targeting and a low background value as well as a dual-function agent in photodynamic therapy still need to be developed.